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Absorbed Dose |
| The amount of a substance that actually enters into the body, usually expressed as milligrams of substance per kilogram of body weight (mg/kg). |
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Absorption |
| The process by which toxicants cross body membranes and enter the blood stream or lymphatic system. Absorption frequently refers to the movement of a chemical from outside the body across membrane barriers to gain entrance into the body. |
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Acetylcholine |
| An important chemical in the body having physiological functions, including the neurotransmission of electrical impulses across synapses of nerve endings. |
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Acetylcholinesterase |
| An enzyme present in nervous tissue, muscle, and red blood cells that catalyzes the hydrolysis of acetylcholine to choline and acetic acid. |
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Acid |
| A substance with one or more hydrogen atoms that are readily replaceable by electropositive atoms. It is a donator of protons. In aqueous solution, it will undergo dissociation with the formation of hydrogen ions. It has a pH of less than 7.0. |
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Active Transport |
| The movement of a substance across a membrane requiring energy. The substance moves against a concentration gradient, from a less concentrated region to a more concentrated region. |
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Acute Effect |
| An effect that occurs almost immediately (hours/days) after a single or brief exposure to a toxic agent. Generally, acute effects will be evident within 14 days. |
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Aerosols |
| Aerosols are suspensions of very small airborne particles of a liquid or solid in a gas. |
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Albumin |
| A simple protein soluble in water and distributed throughout body tissues. It is the most abundant plasma protein. |
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Allergy |
| An immune hypersensitivity reaction of body tissues to allergens that can affect the skin (urticaria), respiratory tract (asthma), gastrointestinal tract (vomiting and nausea) or produce a systemic circulatory response (anaphylactic response). |
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Alveoli |
| The air sacs at the ends of the tracheo-bronchial tree in which gases are exchanged between inhaled air and the pulmonary capillary blood. |
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Anemia |
| A condition in which there is reduced or impaired red blood cells or hemoglobin resulting in an inadequate capacity of the blood to transport oxygen to body tissues. |
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Anoxia |
| An insufficient (below normal) supply of oxygen in body tissues. |
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Antagonism |
| An interaction between two chemicals in which one decreases the expected toxic effect of the other. |
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Antibody |
| An antibody is a protein molecule (immunoglobulin with a unique amino acid sequence) that only interacts with a specific or closely related foreign substances (antigen). The antibody is induced (a response of the immune system) as a result of prior exposure to the antigen. |
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Anticholinergic Effects |
| Neurological effects resulting from the blockage of acetylcholine, which transmits impulses across nerve junctions. |
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Antidote |
| A remedy for counteracting a poison. |
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Aqueous |
| Of a watery nature. Prepared with water. |
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Asphyxiant |
| A substance, that in high concentrations in air, replaces or reduces the oxygen level such that a person inhaling the air mixture suffers hypoxia. |
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Base |
| A substance that dissociates in water to yield a hydroxyl ion. A donator of electrons. |
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Biliary |
| Pertaining to bile, an excretion produced by the liver, stored in the gall bladder, and released into the small intestine. |
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Bioactivation |
| The metabolic process whereby a parent substance is chemically changed to a daughter substance which has increased biological activity. |
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Biological Half-Life |
| The time required to eliminate one-half the quantity of a substance from the body. |
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Biotransformation |
| Conversion of a chemical from one form to another by a biological organism. |
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Blood plasma |
| The non-cellular, fluid portion of whole blood. |
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Body Burden |
| The total amount of a substance which has accumulated in the body. |
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Bone Marrow |
| The tissue within the internal open space of bones (e.g., shaft of long bones) in which the blood-forming elements exist. |
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Bronchioles |
| The very small branches of the tracheo-bronchial tree of the respiratory tract which terminate in the alveoli. |
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Capillaries |
| The very small blood vessels that take blood from small arteries to small veins. |
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Carcinogen |
| A compound which is capable of causing cancer. |
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Carcinogenic |
| The ability of a substance to cause cancer. |
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Carcinogenicity |
| The complex process whereby normal body cells are transformed to cancer cells. |
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Catalyst |
| A substance that accelerates a reaction. |
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Cell membrane |
| The membrane composed of phospholipids, proteins, and cholesterol that form the outer boundary of a cell and regulates the movement of substances into and out of the cell. |
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Cholestasis |
| A liver condition in which excretion of bile salts via the bile duct is inhibited resulting in bile salts backing up into liver cells. |
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Chronic Effect |
| An effect that either shows up a long time after an exposure (the latency period) or an effect that results from a long-term (chronic) exposure. |
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Compartment |
| As used in toxicokinetics, compartment is a hypothetical volume of a body system wherein a chemical acts homogeneously in transport and transformation. The body is composed of organs, tissues, cells, cell organelles, and fluids, any one or several of which may be referred to as a compartment. |
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Concentration Gradient |
| The relative amounts of a substance on either side of a membrane. Diffusion occurs from a region of high concentration to a region of low concentration. |
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Conjugate |
| A metabolite that results form the joining of a Phase II molecule with a xenobiotic. It is generally more water soluble that the original substance. |
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Conjugation |
| A metabolic process in which chemical groups are attached to foreign substances in the body, usually making the conjugated chemical more water soluble and easier to eliminate from the body. |
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Covalent Bond |
| The joining together of atoms that results from sharing electrons. |
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Cytochrome P -450 |
| An iron-protein complex with a maximum absorbance of visible light at 450 nm that functions as a nonspecific enzyme system during Phase I biotransformation reactions. |
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Cytoplasm |
| The fluid matrix of a cell exclusive of the nucleus. Cytoplasm consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it. This is the site of most chemical activities within the cell. |
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Cytosol |
| The liquid medium of the cytoplasm, that is, cytoplasm without the organelles and nonmembraneous insoluble components. |
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Detoxification |
| A metabolic process whereby a parent substance is changed to a daughter product (metabolite) that has lessened toxicity. |
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Diffusion |
| The spontaneous movement of a substance from a high concentration gradient to a lower concentration gradient. |
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Disposition |
| The term used to describe the kinetics of a substance in the body. It encompasses absorption, distribution, metabolism, and elimination of a chemical. |
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Distal |
| Away from a point of reference. As used in medicine, something distal is farther away from the main body. For example, the foot is distal to the knee. |
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Distribution |
| Movement of a substance from the portal of entry to other areas of the body. |
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DNA |
| Deoxyribonucleic acid. The very large molecules in the nucleus of all living cells. It carries the genetic code. |
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Dose |
| The amount of a substance received at one time. Dose is usually expressed as administered or absorbed dose (e.g., milligrams material/kilogram of body weight). |
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Elimination |
| The toxicokinetic process responsible for the removal or expulsion of a substance from the body. |
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Endocytosis |
| The process whereby a substance is engulfed and taken into a cell by an inward folding of the cell membrane, which detaches and moves into the cytoplasm. |
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Enterohepatic circulation |
| Also known as enterohepatic recirculation. The cycling of a substance from the blood into the liver, then into the bile and gastrointestinal tract. This is followed by re-uptake into the blood stream from the gastrointestinal tract, possibly after chemical or enzymatic breakdown. |
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Enzyme |
| A protein formed in living cells that acts as a catalyst for chemical reactions in cells. |
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Enzyme Activation |
| The increase in levels of an enzyme as the result of stimulation by another chemical substance. Same as enzyme induction. |
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Enzyme Inhibitor |
| A substance which causes a decrease in levels of an enzyme. |
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Epidermis |
| The outer layer of the skin. Also known as epithelium. |
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Equilibrium |
| A state of balance. Opposing forces exactly counteract each other. |
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Excretion |
| A process whereby substances (or metabolites) are eliminated from the body. |
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Exposure |
| Contact with a foreign substance, usually by inhalation, ingestion, or skin contact. |
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Exposure Dose |
| The amount of a substance to which a person is subjected. |
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Facilitated diffusion |
| The passage of molecules and ions across a cell membrane with the aid of a specific carrier protein. It is dependent on concentration gradient. |
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Fetus |
| The unborn offspring in the postembryonic period, after major structures have begun to form. In humans this occurs from 8-9 weeks after conception until birth. |
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Filtrate |
| A substance that has passed through a filter. As used in toxicokinetics, it usually pertains to the material that has passed through the glomerulus into the renal tubule. |
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Filtration |
| The passage of a solvent and dissolved substance through a membrane or filter. In excretion, a portion of the plasma and dissolved materials undergo filtration through the glomerular filter (capillary bed). |
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First-pass Effect |
| The biotransformation of a substance in the liver after absorption from the intestine and before it reaches the systemic circulation. |
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Gene |
| The smallest subunit of a chromosome that contains a genetic message. |
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Glomerulus |
| The highly vascular structure in the kidney where much of the fluid portion of the blood (serum) is filtered and passes into the kidney tubules, carrying with it toxins and many other materials present in the serum. |
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Glomerular filtration |
| The first step in urine formation in which blood enters the vascularized glomerulus where water and small molecules are forced by hydrostatic pressure across the glomerular filter and into the filtrate of the Bowman's capsule of the renal tubule. |
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Glucuronidation |
| The process of adding glucuronide to a toxicant or Phase I metabolite during Phase II biotransformation. |
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Glucuronide |
| A glycosidic compound of glucuronic acid. Generally inactive. Constitutes the major portion of some metabolites. |
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Glutathione |
| The tripeptide glutamyl-cysteinyl-glycine. It is found in most tissue, especially the liver. It plays a major role in detoxication and cellular protection. |
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Half-Life |
| The time required for a concentration of a substance in a body fluid (usually blood plasma) to decrease by half. |
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Hepatotoxicity |
| Toxicity of the liver, associated bile duct, and gall bladder. |
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Hepatotoxin |
| A systemic poison whose target organ is the liver. |
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Hydrolysis |
| The chemical process in which water is used to split a substance into smaller molecules. The hydrogen and hydroxyl parts of a water molecule bond to opposite locations on a chemical bond at the site where the split occurs. |
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Hydrophilic |
| Water loving. Substance that has strong polar groups that readily interacts with water. |
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Hypersensitivity |
| A state of altered immune reactivity in which the body reacts with an exaggerated response to a foreign agent. |
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Hypoxia |
| A partial reduction in the oxygen concentration supplied to cells or tissues. |
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Inhibition |
| A reduction in the activity of a reaction. In toxicokinetics, it normally refers to enzyme inhibition. |
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Interstitial fluid |
| The fluid in the space between cells. Same as intercellular fluid. |
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Intracellular Fluid |
| The fluid within a cell. It is also known as the cytoplasm. |
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Ionized |
| Separated into ions. Normally, an ionized substance will dissolve in water. |
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Irritation |
| Local tissue reaction without involvement of an immunologic mechanism. It is a reversible inflammation. |
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Interactions |
| Refers to measures of effects of simultaneous exposure to two or more substances. The four types of interactions are additive, antagonistic, potentiation, or synergistic. |
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Kinetics |
| Refers to turnover, movement or rate of change of a specific factor, e.g., chemical reaction. It is commonly expressed in units of amount per unit time. |
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Latency Period |
| The period of time between an exposure and onset of toxicity. |
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Lipid |
| A large and diverse group of organic compounds that contain primarily carbon and hydrogen atoms with a lesser amount of oxygen. Most lipids are insoluble in water but will readily dissolve in other lipids and in organic solvents. |
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Lipid Soluble |
| Capable of being dissolved in fat or in solvents that dissolve fat. Usually non-ionized compounds. |
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Lipophilic |
| Having an affinity for fats or lipids. A substance that is lipophilic has high lipid solubility and can penetrate cell membranes by passive diffusion. |
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Lipophilicity |
| A term used to describe the ability of a substance to dissolve in, or associate with, fat and therefore living tissue. This usually applies to substances that are non-ionized or non-polar or have a non-polar portion. High lipid solubility usually implies low water solubility. |
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Macrophage |
| Large phagocytic cells of the blood or lymph systems that can engulf particles or small organisms. |
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Mechanism of Action |
| The specific manner by which a substance causes a particular effect. |
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Metabolism |
| The conversion of a chemical from one form to another. It is also known as biotransformation. |
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Metabolite |
| A chemical produced when a substance is metabolized by a biological organism. |
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Mg/kg |
| A commonly used dose that stands for mg of a substance per kg of body weight. |
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Mg/kg/day |
| A commonly used dosage that stands for mg of a substance per kg of body weight on a daily basis. |
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Mg/M3 |
| An exposure unit used to express concentrations of particulates in the air, standing for milligrams of compound per cubic meter of air. |
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Microgram (µg) |
| A commonly used unit of weight consisting of one millionth (1 x 10-6) of a gram. |
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Microsomes |
| The subcellular organelles that are a part of the smooth endoplasmic reticulum. |
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Milligram (mg) |
| The most commonly used unit of measure in medicine and toxicity consisting of one thousandth of a gram (1x10-3 g). |
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Monooxygenase |
| Enzyme system (such as cytochrome P450 ) involved in the oxidation of compounds. |
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Neonates |
| Newborn animals. For humans, it generally refers to the first four weeks of life. |
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Nephron |
| The functional unit of the kidney that produces urine. The primary areas are the glomerulus, convoluted tubule, and collecting duct. |
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Nephrotoxin |
| A systemic poison whose target is the kidney. |
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Non-polar |
| A term used to describe a molecule, which is neutral or possesses neither a positive or negative charge. |
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Octanol/Water Partition Coefficient |
| The ratio of the amount of a substance that will dissolve in octanol versus the amount that will dissolve in water. The higher the octanol/water partition coefficient the greater the tendency of substance to be stored in fatty tissues. |
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Organelle |
| A subcellular structure such as the mitochondria or nucleus of a cell. |
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Oxidation |
| A change in a chemical characterized by the loss of electrons. This is a primary Phase I type biotransformation reaction. |
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Partition Coefficient |
| see Octanol/water partition coefficient. |
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Passive Transfer |
| The movement across a membrane by simple diffusion. This is the most common way lipophilic xenobiotics pass through cell membranes. |
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Percutaneous absorption |
| The transfer of a substance from the outer surface of the skin through the corneum and outer layers and into the systemic circulation. |
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Phagocytosis |
| The engulfing of particles by certain cells of the circulatory and lymphatic systems, known as phagocytes. Phagocytosis is a primary cellular defense mechanism against foreign particles or organisms. |
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Pharmacokinetics |
| Quantitation of the time course of chemical absorption, distribution, metabolism, and elimination. |
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Phospholipids |
| Molecules containing phosphates and lipids found in the cell membrane. The phosphate head is hydrophilic, whereas the lipid tail is hydrophobic. |
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Pinocytosis |
| The process whereby a liquid is engulfed and taken into a cell by an inward folding of the cell membrane, which detaches and moves into the cytoplasm. |
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Plasma |
| The non-cellular, fluid portion of whole blood. |
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Plasma membrane |
| The membrane composed of phospholipids, proteins, and cholesterol that forms the outer boundary of a cell and regulates the movement of substances into and out of the cell. Same as "cell membrane." |
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Polar |
| A term used to describe a molecule which is charged or ionized. Polar substances are usually the easiest for the body to excrete. |
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Portal circulation |
| The term applied to the venous circulation draining the tissues of the gastrointestinal tract into the liver. |
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PPM |
| Parts per million - the number of units of a substance in a million units. PPM is a common concentration unit for dilute samples of dissolved substances or airborne substances. |
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Protein |
| A complex nitrogenous substance which constitutes the main building material in cells. |
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Reduction |
| A change in a chemical characterized by the gain of electrons. This is one of the main Phase I biotransformation reactions. |
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Secretion |
| A process in which molecules are actively transported out of an organ. |
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Solubility |
| Ability of a substance to be dissolved in a solvent. The solubility is expressed according to the solvent, e.g., water solubility, solubility in acetone, etc. |
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Substance |
| Physical material of which something is made. It may be element, compound, or a mixture of materials. |
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Substrate |
| A substance acted upon. It often refers to the chemical that undergoes reaction with an enzyme. |
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Systemic toxin |
| A toxin that affects the entire body or many organs. |
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Target Organ |
| An organ in which a xenobiotic exerts a toxic effect. |
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Threshold Dose |
| The dose at which a toxic effect is first encountered. |
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Total Dose |
| The sum of all individual doses, which may be received over a period of time. |
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Toxicant |
| An agent that produces adverse effects when absorbed into the body. |
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Toxicokinetics |
| The study of the time-dependent processes related to toxicants as the interact with living organism. It encompasses absorption, distribution, storage, biotransformation and elimination. |
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Toxicology |
| The study of the harmful interactions of chemicals on living organisms and biological systems. |
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Toxin |
| A specific protein produced by certain plants, animals and microorganisms that is highly toxic to other organisms (snake venom). |
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Vapor Pressure |
| The pressure exerted when a solid or liquid is in equilibrium with its own vapor. The higher the vapor pressures the higher the volatility. |
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Volatility |
| The ability of a substance to change from liquid or solid form to a gaseous form. |
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Volume of distribution (VD) |
| The volume of body fluid in which a compound is apparently distributed. It may consist of plasma, interstitial fluid, and intercellular fluid. |
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Xenobiotic |
| A chemical foreign to the body. It is a chemical that is not endogenous or present in the body under normal conditions. |
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